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To determine whether the use of a hydrocolloid nasal barrier dressing during binasal continuous positive airway pressure (CPAP) therapy, compared with no barrier dressing, reduces the rate of nasal injury in very preterm and/or very low birth weight infants.A single-center randomized controlled trial conducted in the neonatal intensive care unit at The Royal Women's Hospital, Melbourne. Eligible infants were born <30 weeks of gestation and/or with birth weight <1250 g, and had received ≥4 hours, but <48 hours, of CPAP. Infants were randomly allocated to receive either a hydrocolloid nasal barrier dressing during CPAP (barrier group), or no barrier dressing (no barrier group). The primary outcome was the incidence of any nasal injury during CPAP support, until the infant was both >30 weeks of postmenstrual age and >1250 g, unless CPAP therapy was stopped earlier. Nasal injury was regularly assessed by bedside nurses using a standardized form.A total of 108 preterm infants were enrolled: 53 infants in the barrier group and 55 infants in the no barrier group. Infants in the barrier group had a significantly lower rate of nasal injury compared with the no barrier group: 18 of 53 (34%) vs 31 of 55 (56%), respectively (P = .02), number needed to treat; 5 infants. No significant differences were detected in any secondary respiratory outcomes, or in the rate of common neonatal morbidities.Prophylactic use of a nasal barrier dressing within 48 hours of commencing treatment with binasal CPAP in very preterm or very low birth weight infants reduces nasal injury.Australian and New Zealand Clinical Trials Register ACTRN12616000438459.